This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Using Molecular Dynamics (MD) simulations, computational protein modifications, and a novel theoretical methodology that determines structural rigidity/flexibility, we will concentrate on studying the family of ionotropic glutamate receptors (iGluR) due to their medicinal and biological importance. Also, we will continue to investigate the ion channel proteins with known and unknown tertiary structure. We will correlate flexibility of the protein structure with its functional characteristics, such as ion permeation and selectivity in open channels, and conformational rearrangements in gating. We are planning to analyze stability, i.e. rates and dynamics of formation and breakage of hydrogen bonds and hydrophobic contacts in protein systems that differ by size, flexibility, and a shape of ligand-binding cavities.